The lipocalin family is a large group of small extracellular proteins, having a great diversity at the sequence level. Despite the sequence dissimilarity, their structures are highly conserved.
Based on the conservation of three structurally conserved regions (SCRs), they are divided into two groups. The core set of lipocalins, called ‘kernel’, are quite closely related proteins and share the three SCRs. The more divergent lipocalins, called outliers, match no more than two of the SCRs.
The lipocalins exhibit great functional diversity. They are implicated in modulation of the immune response, regulation of cell homoeostasis and in the clearance of endogenous and exogenous compounds. They have roles in retinol and pheromone transport, olfaction, invertebrate coloration and prostaglandin synthesis.
Lipocalins have been shown to bind a number of molecules implicated in homeostasis, as retinoids, arachidonic acid and various steroids, in message transmission between individuals as pheromones, in olfactory and gustatory functions and in pigmentation. A small ligand can be enclosed deep within the cavity, while bigger ones interact with the upper loops and even protrude out of the protein to interact with the solvent. Some lipocalins seem to be adapted to the recognition of an individual ligand, while others can bind a broad diversity of molecules.
In addition, eicosanoids are potent lipid mediators involved in inflammation and derived from phospholipase-released arachidonic acid. These include leukotrienes, prostaglandins, thromboxanes, prostacyclins and lipoxins. Leukotrienes are predominantly synthesised by inflammatory cells like granulocytes, mast cells and macrophages.
Four major leukotrienes are implicated in inflammation, i.e. leukotriene B4, C4 (LTC4) and D4 (LTD4) and E4 (LTE4).
LTB4 is a potent chemotactic factor for neutrophils. It also induces their activation, causing degranulation and superoxide generation. Additionally, it participates to the trafficking of T lymphocytes, it enhances macrophage and neutrophil phagocytosis, and promotes the elaboration of other inflammatory mediators, such as cytokines and chemokines. Furthermore, experimental and genetic studies suggest a major role of leukotrienes in atherosclerosis and in its ischemic complications such as acute coronary syndromes and stroke.
Several lipocalins, implicated in the modulation of the host hemostatic and inflammatory systems, have been identified in blood sucking arthropods. Lipocalins in Rhodnius prolixus were shown to bind serotonin, ADP, NO and in Rhipicephalus appendiculatus, three were shown to bind histamine; but no one appeared to bind leukotriene B4.
Publication from Francischetti et al (Insect Biochemistry and Molecular Biology, Elsevier Science Ltd, volume 35, nr 10, pages 1142-1161, 2005) describes putative secreted histamine-binding proteins.
It would thus appear that said molecule, which upon successful expression, would constitute appropriate antigens for anti-tick vaccines and/or new therapeutic agents.